In a complex auditory scene, a listener is confronted with multiple interleaved sequences of sounds that must somehow be assigned to corresponding sound sources. This process is referred to as stream segregation, where each stream represents the perceptual correlate of a sound sequence from a particular source. Spatial separation of sound sources facilitates the recognition of multiple sequences of sounds (i.e., multiple streams) as belonging to distinct sources. A central question in auditory neuroscience is how auditory streams are formed in the brain. The goal of this proposal is to further explore the cortical correlates of spatial stream segregation, as well as uncover their cellular mechanisms. While cats have been favored as experimental models for spatial hearing research, they are impractical for in vivo intracellular and pharmacological experiments. Instead, small rodents like the rat are well-suited for these kinds of studies. Thus, we have chosen the rat, rather than the cat, as a model for the proposed research. In order to achieve the goal of elucidating the cellular mechanisms of spatial stream segregation, we propose three specific aims: 1) Evaluate the spatial sensitivity of rat primary auditory cortex (A1); 2) Characterize spatial stream segregation in rat A1; 3) Determine the neural mechanisms of spatial stream segregation in rat A1. Aim 1 will utilize extracellular techniques to assess the spatial sensitivit of rat A1 units to noise burst stimuli presented from free-field speaker locations that vary 360-deg across azimuth. Aim 2 will implement a spatial stream segregation paradigm adapted from a previous psychophysical study performed in our lab. Cortical responses will be recorded with extracellular techniques and analyzed with innovative methods and computational models. Aim 3 will combine extracellular recordings with the pharmacological blockade of GABAA receptors to determine the role of intra-cortical inhibition in spatial stream segregation. This proposal wil investigate, for the first time, whether the intra-cortical inhibitory effects by GABAA receptors account for spatial stream segregation in A1. Our examination of the potential intra-cortical mechanisms that may take part in the formation of auditory streams will advance our understanding of how auditory scene analysis is accomplished in A1. Specifically, which characteristics are synthesized de novo in the cortex, enhanced by cortical processing, or passively inherited from subcortical inputs? Elucidating mechanisms responsible for various aspects of spatial stream segregation have broad implications in aiding the design of sound processing schemes for enhanced hearing in complex auditory scenes by users of hearing aids and cochlear implants.